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Weight gain is a common, but often overlooked side effect to many widely used drugs. In susceptible individuals the weight gain may result in clinically significant obesity and associated comorbidities. Both tricyclic antidepressant medications and antipsychotic compounds are those prominently cited for producing persistent and problematic body weight gain in many treated patients and have a serious impact on medication compliance to an otherwisebeneficial treatment.Furthermore,weight gain is often seen as an improvement of the psychiatric disease and therefore not recognized before the initial body weight is exceeded by several kilos. The mechanisms behind the weight gain are poorly understood.Many of these drugs interfere with central appetite-regulating neurotransmitters and may also produce sedative and anticholinergic effects, ultimately contributing to changes in energy expenditure. The incidence of weight gain during acute and chronic treatment with different classes of frequently prescribed drugs will be reviewed (Table 19.1), as will the possiblemechanisms by which such drugs alter energy intake and expenditure, contributing to drug-induced weight gain (Table 19.2). Newer, effectivemedication classes, without the side effect of weight gain will also be discussed. ANTIDEPRESSANT MEDICATIONS